Drug Interaction Report

Coadministration with inhibitors of the isoenzyme CYP450 3A4 may increase the plasma concentrations and effects of maribavir, a CYP450 3A4 substrate. When a single 400 mg dose of maribavir was administered with a single 400 mg dose of ketoconazole, a potent CYP450 3A4 and P-glycoprotein (P-gp) inhibitor, mean maribavir peak plasma concentration (Cmax) and total systemic exposure (AUC) increased by 10% and 53%, respectively, in 19 study subjects. These changes are not considered clinically significant. No dosage adjustments are necessary when maribavir is prescribed with CYP450 3A4 inhibitors, but it may be advisable to monitor patients for maribavir-related adverse effects such as taste disturbances, nausea, diarrhea, vomiting, and fatigue.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.